Project Summary/Abstract Despite the availability of ever more potent antiretroviral therapy, the struggle to optimize the health of HIV- infected men and women continues, as they suffer and die from premature medical co-morbidities including cardiovascular, pulmonary disease, neurocognitive dysfunction and malignancies. The goal of the Chicago Cook County Clinical Research Site (CRS) of the MACS/WIHS Combined Cohort Study, formerly the Chicago Women's Interagency HIV Study, is to advance understanding of HIV-related co-morbidities and pathogenesis through scientific innovation and a translational approach involving investigators from basic, clinical, behavioral and community health sciences. In collaboration with the other national Clinical Research Sites and the Data Analysis and Coordinating Center, the site has developed a Unified Science Agenda that aims to holistically describe mechanisms underlying premature morbidity and mortality in HIV-infected persons. Cook County CRS investigators will lead or co-lead projects in Behavioral Science, Malignancy, Neurocognition, Sleep Science and Pathogenesis including initiatives related to Liver Disease, Oral Health, Microbiome Science and Outcome Adjudication. The Cook County CRS will contribute to HIV and multidisciplinary science by fostering collaboration through an open, inquisitive approach, sharing ideas and the rich data and specimen resources of the cohort with qualified experts who can further advance mechanistic understanding of HIV- associated co-morbidities. The Cook County CRS will also support promising and diverse early career investigators and those new to HIV research through pilot grants, intentional mentorship, and linkage to resources to support independent funding. Finally, through expansive engagement of cohort participants and community partners, the Cook County CRS will rapidly disseminate key study findings and obtain insight into the most pressing issues for Chicagoans affected by HIV to inform future scientific direction.